ABSTRACT
BACKGROUND: Synthetic cathinones (SCs) are a large category of new psychoactive substances (NPS), which pose a serious threat to public health due to limited information about their toxicology and pharmacology. Many SCs are closely related in their chemical structures, with some substances being positional isomers. In this study, we propose a new workflow for the identification of SC isomers using liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS2) combined with electron activated dissociation (EAD) and chemometrics. Differentiation between isomeric SCs is essential for both legislative and public safety reasons, since minor differences in their molecular structures may change their legal status and pharmacological profiles. RESULTS: The workflow was optimized using ring-substituted isomers of methylmethcathinones, methylethcathinones, and chloromethcathinones. The kinetic energy in the EAD cell was investigated at three levels (i.e., 15, 18, and 20 eV) for each group. Two data analysis methods (i.e., t-distributed stochastic neighbor embedding [t-SNE] and a Random Forest [RF] algorithm) were applied using the obtained EAD mass spectral data. The three sets of ring-substituted SCs were clearly distinguished using t-SNE and an RF algorithm. Moreover, the RF approach resulted in a 97 % classification accuracy for isomer identification using various combinations of compounds, isomers, and electron kinetic energies. This workflow was subsequentially applied to the analysis of 26 blind street samples, resulting in a 92 % classification accuracy for isomer identification. However, the accuracy varied based on the kinetic electron energy. A subset of the original data set, focusing on 15-eV data only, was used, resulting in a classification accuracy of 100 %. SIGNIFICANCE: This study presents the first LC-HRMS2 workflow based on EAD and chemometrics, which resulted in a classification accuracy of 100 % of authentic street samples. The developed LC-HRMS2 workflow demonstrates that EAD product ions and their characteristic ion ratios can be successfully used to identify ring-substituted positional isomers of SCs.
ABSTRACT
BACKGROUND: In this article, we present an evaluation of online psychoactive substance trade via Telegram, a free encrypted social media messenger service. The evaluation took place during the COVID-19 pandemic, which allowed us to monitor the effects of the spring 2020 lockdown in the Netherlands on substance trade via Telegram. OBJECTIVE: The objective of this study was to evaluate whether changes in psychoactive substance trade on Telegram markets in the Netherlands can be observed during the COVID-19 pandemic. RESULTS: Between December 2, 2019, and June 29, 2020, a total of 70,226 posts appeared in two analyzed Telegram groups. A total of 5,643 posts were psychoactive substance related. Based on the analyzed posts, Telegram is mostly a '"sellers" market as only a minority of the posts (6.3%) could be identified as a request for a substance. The proportion of posts related to specific substances varied between the periods before, during, and after the lockdown. The proportion of posts on the stimulants ecstasy, cocaine, and amphetamine was lower during the lockdown than before and after. For psychedelics - ketamine, lysergic acid diethylamide (LSD), and 2,5-dimethoxy-4-bromophenethylamine (2C-B) - and other substances, there was a relative increase in the number of posts during the lockdown, which was maintained after the lockdown. CONCLUSIONS: Telegram analysis shows that in the Netherlands, online psychoactive substance trade may have been affected during the COVID-19 pandemic. The direction of this effect was different for different classes of substances.